Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis

In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II) –induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is th e first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrov ascular rupture during the ICH process.
Source: Translational Stroke Research - Category: Neurology Source Type: research